Human granulocytic ehrlichiosis (HGE) is caused by a remarkable pathogen, first isolated in our laboratory, A. phagocytophila, which is remarkable in its ability to bind to and infect human white blood cells, and, particularly, the human neutrophil (PMN), which is the main cell that normally kills invading bacteria. We have elucidated several steps in HGE binding to and survival in PMN and in related cell lines, including the cellular receptor (P-selectin glycoprotein-1), and the activity of A. phagocytophila in preventing cell death, thus allowing survival of infected cells. These and several other unique properties of A. phagocytophila are under study in our lab using multiple approaches, including microarray analysis. By defining early events in A. phagocytophila interaction with PMN, we are using the microbe as a tool to understand the biology and function of PMN, a critical cell in defense against a variety of infections, including potential agents of bioterrorism. These studies, through further characterization of HGE:cell interactions, should also offer insights into normal and abnormal human inflammation in health and disease. These studies are also defining normal and abnormal gene expression in PMN, which should help to assure and potentially improve the quality of PMN and related cells used in blood transfusion and in cell and gene therapies. In addition, in collaboration with investigators at the University of Minnesota, we continue to study HGE interactions with human endothelial cells and with tick cells.